Protecting from invaders and surveilling for other threats is a big job—and it’s what your immune system, your body’s very own built-in defense mechanism, does every day. When you catch a cold or other viral infection, for instance, your immune system mounts a response that mobilizes killer T cells and triggers the release of antibodies, which identify the virus as harmful and destroy it. Mission accomplished. Your immune system then quiets back down and you feel better.
If you have an autoimmune condition, however, that’s not what happens.
Instead, your immune system mistakenly treats your body’s normal tissue as an invader and attacks it, which causes chronic inflammation. Research published in The Lancet in 2023 suggests one in 10 people around the world live with an autoimmune disease, an umbrella term that pertains to over 100 conditions, including well-known ailments like rheumatoid arthritis, psoriasis and ulcerative colitis, as well as many lesser-known ones such as Sjogren’s disease and myasthenia gravis. The impact varies by disease, but patients typically develop symptoms that can be painful and debilitating and take a significant toll on quality of life.
Johnson & Johnson has a long history of innovating to help advance treatments for autoimmune diseases. With the introduction of anti-TNF (or tumor necrosis factor) therapies 25 years ago, the company pioneered a revolution that helped define a new standard of care. Since then, Johnson & Johnson has distinguished itself by consistently redefining that standard of care—focusing on diseases where there remains a significant unmet need.
Patient need is the key. Despite these decades of advancements, fewer than 10% of people with an autoimmune disease are able to reach durable remission even on advanced therapies. Some don’t benefit from current therapies at all, while a sizable subset respond at first, but then ultimately relapse. That’s why scientists at Johnson & Johnson are continuing to develop and refine new options aimed at getting more patients into remission and keeping them there.
“The ultimate goal is restoring health for all patients with autoimmune diseases,” says David M. Lee, M.D., Ph.D., Global Immunology Therapeutic Area Head for Johnson & Johnson Innovative Medicine. “You could say that’s audacious, but we’re well on the journey toward reaching that goal.” Here’s how.
By focusing on the underlying immune pathways that cause disease
Johnson & Johnson’s pathway approach to developing new medicines, in combination with deep knowledge relating to specific diseases, enables the company to impact many diseases with a single therapy.
Take, for example, psoriasis and inflammatory bowel disease (IBD)—two very different conditions. Psoriasis is a chronic inflammatory condition that primarily impacts the skin; in IBD, the inflammation and disease are concentrated in the digestive tract. But scientists know that a specific inflammatory cytokine (protein) called interleukin-23 (IL-23) plays a significant role in both conditions.
“Several of our therapies have shown success in selectively targeting this cytokine, and we have set a high bar of assessing clinical and tissue level remission in our clinical trials,” says Dr. Lee.
“Through this pathway approach, we’re advancing treatments that can help provide meaningful improvements in rates of remission across several disease areas, including psoriasis, psoriatic arthritis and inflammatory bowel disease,” says Candice Long, Worldwide Vice President for the Immunology Therapeutic Area, Johnson & Johnson Innovative Medicine.
“While the currently available biologic drugs that block IL-23 are effective for many patients, fewer than 30% of moderate to severe plaque psoriasis patients who are eligible for these medications opt to take them,” says Dr. Lee.
Why?
“Many aren’t comfortable using a biologic therapy because they dislike injections or have a perceived risk of intravenous and injectable treatments,” says Long. Work is underway to develop treatment options in the convenience of a pill.
The IL-23 pathway is a pathogenic driver in diseases like psoriasis, psoriatic arthritis and IBD. Psoriasis is an immune-mediated disease well known for causing scaly plaques, which can be itchy and painful and also take a major toll on self-esteem and overall quality of life. What’s more, this condition causes inflammation throughout the body, and patients have higher rates of serious medical complications like heart attacks and strokes. A substantial number of psoriasis patients also develop psoriatic arthritis, which causes joint pain and deformities if untreated.
“We are committed to helping redefine the standard of care and address the unmet needs and preferences of many patients living with plaque psoriasis,” explains Long, citing findings that were recently published in The New England Journal of Medicine.
By testing a new combination drug for ulcerative colitis patients
People with moderate to severe ulcerative colitis are often given biologics that target a different inflammatory cytokine than IL-23 called tumor necrosis factor (TNF). The problem: Up to 30% will not respond to these medications, and another 23 to 46% will initially respond, only to have the drug stop working. A similar number of these patients try and fail with biologics that focus on IL-23.
“Now, a brand new co-antibody therapy is being developed to target TNF as well as IL-23,” says Dr. Lee.
With single-agent drugs, many patients experience a plateau effect, but combination therapy has the potential to break through the “therapeutic ceiling,” so patients stay well, adds Dr. Lee. “Our deep disease expertise and experience uniquely position us to identify effective combinations. Our goal is to reach patients who aren’t achieving remission—including a large population of individuals who have experienced inadequate results from advanced therapies.”
By controlling allo- and autoantibodies to treat a range of diseases
The most common antibody is immunoglobulin G (IgG) and the body uses it to fight off invaders such as bacterial and viral infections. If you contract COVID-19, the flu or any other contagious ailment, for instance, your body will start making IgG about 24 to 48 hours later. But if you have an autoantibody disease—a subset of autoimmune diseases—your body produces pathogenic IgGs, also known as autoantibodies, that attack its own critical organs and tissues; in pregnant individuals, maternal alloantibodies can attack the organs and tissues of the fetus.
With nearly 240 million people worldwide suffering from severe autoantibody diseases, including several rare conditions that lack adequate or in some cases any advanced treatment options, Johnson & Johnson is leading research for potential treatments in three key segments. These include rare autoantibody diseases like myasthenia gravis, which affects the neuromuscular junction; maternal-fetal immune disorders mediated by maternal alloantibodies like hemolytic disease of the fetus and newborn, a condition which occurs when the blood types of a pregnant individual and the fetus are incompatible; and rheumatic diseases like Sjogren’s disease, in which the immune system attacks the moisture-secreting glands and mucous membranes, resulting in dryness wherever the body naturally self-lubricates, such as the mouth and eyes.
“We are just at the beginning of this journey,” explains Dr. Lee. “We have a relentless dissatisfaction with treatment options that fall short of durable remission, and we know that millions of patients are waiting for scientific advancements. That’s an opportunity and responsibility that motivates our team every day.”
